MD
Emilie Erbs
Department of Clinical Genetics, Vejle Hospital.
| Projekt styring | ||
| Projekt status | Open | |
| Data indsamlingsdatoer | ||
| Start | 01.09.2025 | |
| Slut | 31.12.2035 | |
Monogenic disorders in patients with childhood-onset nephrolithiasis/nephrocalcinosis
Short summary
The purpose of the project is to describe the monogenic causes of nephrolithiasis and nephrocalcinosis among children in Denmark by establishing a database of patients who have undergone genetic testing. We aim to examine the diagnostic yield of genetic testing and characterize the disease burden and associated clinical manifestations in patients with underlying monogenic causes. We will furthermore evaluate the clinical impact of genetic testing for both the affected children and their families
Rationale
Background Nephrolithiasis and nephrocalcinosis can lead to both acute and chronic pain, urinary tract infections, reduced kidney function, and, in severe cases, a need for dialysis or kidney transplantation. Unlike adults, children often have an underlying metabolic, syndromic, or anatomical cause that predisposes them to the formation of kidney stones or calcification. As a result, they are at increased risk of recurrent episodes and impaired kidney function. Genetic testing can help reach a faster and more accurate diagnosis, providing a clear explanation for the patient's condition and more precise prognostic information. In addition, a specific genetic diagnosis allows for the use of targeted treatments and follow-up plans that are tailored to the complications associated with the particular genetic disorder. Genetic testing can also have broader implications for the patient's family. It may lead to genetic screening of asymptomatic relatives, allowing early preventive measures to be implemented. It can also help in selecting non-carrier kidney donors within the family and in providing reproductive counseling, including information on prenatal diagnostic options. Previously, the use of genetic testing of these patients has been limited, primarily due to the high costs and limited availability of comprehensive analysis methods. However, with recent advances in genetic technologies, genetic testing has become more accessible and cost-effective. Today, it is possible to offer whole genome sequencing (WGS) based analyses as part of the routine diagnostic evaluation. Despite this progress, there is still limited knowledge regarding the monogenic causes of nephrolithiasis and nephrocalcinosis among children in Denmark. No large-scale Danish studies have previously been conducted thus the prevalence of monogenic causes remains unknown. And knowledge of the clinical impact of genetic testing for these children and their families is limited. Results and Perspectives By establishing a database of patients with childhood-onset nephrolithiasis or nephrocalcinosis who have undergone genetic testing, it becomes possible to systematically record clinical characteristics and diagnostic findings. Data from the database will shed light on the diagnostic yield of genetic testing, as well as map hereditary conditions, related clinical manifestations, and disease burden. Furthermore, we will evaluate the clinical impact of genetic testing. Both by determining wether the genetic diagnosis alters the clinical diagnosis or leads to changes in follow-up or treatment of the patient, and by examining if the genetic diagnosis prompts genetic evaluation and monitoring of relatives. Based on previous studies that have used less comprehensive analysis methods compared to WGS-based analyses, we expect that more than 30% of patients will have an underlying monogenic cause. Additionally, we hypothesize that a specific genetic diagnosis will have clinical significance for most patients or their relatives. The results of this project will contribute to understanding the relationship between the underlying molecular genetic mechanisms and the clinical presentation and disease burden of monogenic conditions associated with nephrolithiasis or nephrocalcinosis in children. Moreover, the database may serve as a foundation for other projects, such as investigating of specific monogenic conditions, further evaluation of patients without an identified monogenic cause, or those with variants of unknown clinical significance where the diagnosis remains unclear.
Description of the cohort
Patients with childhood-onset nephrolithiasis/nephrocalcinosis. Patients are recruited from the Department of Urology at Lillebælt Hospital in Vejle. All patients with childhood-onset nephrolithiasis/nephrocalcinosis defined as onset ≤ 18 years of age are offered participation regardless of current age or whether genetic analyses have previously been performed.
Data and biological material
With written consent health information from patient journals is registered in an electronic database i REDCAP: Age at diagnosis, gender, etnicity, consanguinity, disease burden of kidney stones, calcium deposition in the kidney tissue, co-morbidity, blood tests, urine analyses, stone analyses, genetic tests, imaging, medical and surgical treatment and planned follow-up.
Collaborating researchers and departments
Department of Urology, Vejle Hospital